3-(1H-Tetrazol-5-yl)-4(3H)-quinazolinone and related compounds have been described in U.S. Pat. No. 4,419,357 as useful as mediator release inhibitors. The compounds are prepared by a several-step procedure starting with an appropriate 2-nitrobenzoyl chloride. The indicated acid chloride is reacted with 5-aminotetrazole to give the corresponding carboxamide and the nitro group is then reduced to give the corresponding 2-amino-N-(1H-tetrazol-5-yl)benzamide. This benzamide is then heated with triethoxymethane to give the quinazolinone referred to originally. This procedure is generally similar to one described in the literature for preparing other related quinazolinones. While this method may ordinarily be adequate for obtaining the compound in question, it does suffer from a number of disadvantages, particularly when larger supplies of compound are desired. Thus, the nitrobenzoyl chloride starting material used in the original procedure is relatively expensive and reactive; solids handling problems are involved with the intermediates in question and the overall yield is only about 50%.
Other different methods for the preparation of substituted 4(3H)-quinazolinones have been described in the literature and one general approach makes use of anthranilic acid derivatives. Thus, Levy et al., J. Chem. Soc., 1956, 985, describes the reaction of methyl anthranilate with a benzimidoyl chloride to give a quinazolinone. A number of intermediates are suggested although they are not specifically isolated. A similar procedure is described in Bayer German Pat. No. 1,809,174, although the intermediates proposed there are not the same as those set forth by Levy et al. In both of these procedures, however, the benzimidoyl chloride used as a starting material would be relatively stable and easy to prepare as compared to the intermediate formimidoyl chloride which would be needed to prepare the tetrazolyl compounds mentioned earlier. Actually, it is questionable whether the appropriate formidoyl compound could be obtained at all for the indicated tetrazole series.
In a somewhat different approach, Rajappa et al., Tetrahedron, 29, 1299 (1973), describes the reaction of anthranilic acid with a bicyclic imino ether to give a complex tetracyclic system which contains the quinazolinone structure. Rajappa et al., were interested in other questions and provided no details with regard to this process or any background leading up to their use of it. It is noted, however, that their process was limited to the acid (anthranilic) and heat alone was sufficient to bring about the cyclization involved in the preparation of the Rajappa compounds.
Finally, in a still different approach, Arques et al., Anales de Quimica, 156 (1982), describes the reaction of methyl anthranilate first with the dimethylacetal of dimethylformamide followed by an amine to give a 3-substituted 4(3H)-quinazolinone. Arques also provides a brief summary of other methods for preparing 4(3H)-quinazolinones.